I am not sure I understand your question.
Are you saying that you would like your normalization method to be "ratio to heavy", but the amount of heavy that was spiked into each sample depends on the condition?
One thing that you could do is an ordinary Group Comparison in Skyline, using the normalization method "Ratio to Heavy". But, then, you would need to manually multiple the fold change results that Skyline gives you by a factor which depends on the heavy concentration in the two samples.
Is that what you are asking?
If you would like, you can send us your Skyline document and we might understand better what you are asking.
In Skyline you can use the menu item:
File > Share
to create a .zip file containing your Skyline document and supporting files including extracted chromatograms.
If that .zip file is less than 50MB you can attach it to this support request.
Otherwise, you can upload it here: